Journal article
Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies
- Abstract:
- Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.0MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-018-07867-7
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 10
- Article number:
- 29
- Publication date:
- 2019-01-03
- Acceptance date:
- 2018-12-03
- DOI:
- ISSN:
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2041-1723
- Pmid:
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30604766
- Language:
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English
- Pubs id:
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pubs:958252
- UUID:
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uuid:325f32f7-3aa0-41fb-8885-9a7fc47142ad
- Local pid:
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pubs:958252
- Source identifiers:
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958252
- Deposit date:
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2019-01-16
- ARK identifier:
Terms of use
- Copyright holder:
- Morris et al
- Copyright date:
- 2019
- Notes:
- Copyright © 2019 The Authors. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
- Licence:
- CC Attribution (CC BY)
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